DESCRIPTION, OVERALL (provided by applicant): The central goal of the Yale Center of Excellence in Molecular Hematology is to facilitate ongoing collaborative research designed to understand and manipulate gene expression and regulation related to the self-renewal, proliferation and differentiation of hematopoietic stem cells along various pathways to produce diverse blood cell derived lineages, and to explore the more recently recognized plasticity of these and other marrow-derived stem cells. The structure of the Center is predicated on the evolving critical need of a group of 25 highly productive investigators to combine novel technologies designed to understand the functional relationships between chromatin structure and mRNA and protein expression, by facilitating experimentation on highly purified and well-characterized stem cell subpopulations (both murine and human), and to do so with newly created informatics technology that can clarify and classify the meaning of changes in hundreds or even thousands of parameters resulting from a single experiment. The Center will therefore include three cores: Stem Cell Preparation &Analysis, Gene Expression &Genomic Analysis, and Bioinformatics &Biostatistics. The value of these Cores will be leveraged by their close interaction with existing core facilities at Yale including the W.M. Keck Foundation Biotechnology Resource Laboratory, the Yale Center for Excellence in Genomics and Proteomics, the Yale Cancer Center and Yale's new Center for High- Performance Computation in Biomedicine. The Cores will be designed to be highly interactive and to take advantage of new methodologies including chromatin immunoprecipitation and study of gene expression using novel genomic DMA microarrays. The Cores will not be limited to providing technology but will be structured to provide ongoing intensive training to the participating investigative groups. In addition to the scientific Cores, the Administrative Core will aim to enhance and expand research in molecular hematology by providing a small pilot project program for new investigators and for well-established researchers newly entering these areas and by supporting regional seminars on hematopoietic development, plasticity, chromatin structure and relevant informatics with the goal of rapid dissemination of critical knowledge to and from the wider hematologic community.